title: Investigations on collectin liver 1.
abstract: Collectins are pattern recognition molecules of the innate immune system showing binding to carbohydrate structures on microorganisms in a calcium-dependent manner. Recently, three novel collectins, collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1 and CL-11), and collectin placenta 1 (CL-P1), were discovered. The roles of these three collectins remain largely unknown. Here, we present a time-resolved immunofluorometric assay for quantification of CL-L1. The concentration of CL-L1 in donor plasma (n = 210) was distributed log-normally with a median value of 3.0 μg/ml (range 1.5-5.5 μg/ml). We observed on average 30% higher concentrations of CL-L1 in plasma as compared with serum. Size analysis by gel-permeation chromatography showed CL-L1 in serum to elute as large 700-800-kDa complexes and smaller 200-300-kDa complexes. CL-L1 showed specific binding to mannose-TSK beads in a Ca(2+)-dependent manner. This binding could be inhibited by mannose and glucose, but not galactose, indicating that CL-L1 binds via its carbohydrate-recognition domain and has ligand specificity similar to that of mannan-binding lectin. Western blot analysis of CL-L1 showed the presence of several oligomeric forms in serum. Ontogeny studies showed CL-L1 to be present at birth at near adult levels. CL-L1 levels exhibit low variation in healthy adults over a 1-year period. During acute-phase responses, the CL-L1 levels display only minor variations. In serum, CL-L1 was found in complexes with mannan-binding lectin-associated serine proteases, suggesting a role in the lectin pathway of complement activation. The presented data establish a basis for future studies on the biological role of CL-L1.
authors.affiliation: Department of Biomedicine, Wilhelm Meyers Allé 4, Faculty of Health Sciences, Aarhus University, 8000 Aarhus C, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Axelgaard
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Jensen
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Dyrlund
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Enghild
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Jens C
authors.initials: JC
authors.lastname: Jensenius
mesh_terms: D000328:Adult; D037222:Collectins / Q000097:blood*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D057809:HEK293 Cells; D006601:Hexoses / Q000097:blood; D006801:Humans; D008297:Male; D055503:Protein Multimerization; D044967:Serum / Q000378:metabolism*
chemical_list: C445459:COLEC10 protein, human; D037222:Collectins; D006601:Hexoses
keywords: Collectins; Complement System; Inflammation; Innate Immunity; Lectin